Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) Trial

Ischemic Attack, Transient Clinical Trial

— POINT  

Official title:

Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) Trial

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00991029
• Other study ID #: 1U01S062835-01A1
• Status: Terminated
• Phase: Phase 3
• Start date: May 28, 2010
• Est. completion date: April 9, 2018

Study information

• Verified date: November 2018
• Source: University of California, San Francisco
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A transient ischemic attack (TIA) is a transient episode of neurological dysfunction caused by focal brain, spinal cord, or retinal ischemia, without acute infarction. An ischemic stroke is a cerebral infarction. In POINT, eligibility is limited to brain TIAs and to minor ischemic strokes (with an NIH Stroke Scale [NIHSS] score less than or equal to 3).

TIAs are common [25], and are often harbingers of disabling strokes. Approximately 250,000-350,000 TIAs are diagnosed each year in the US. Given median survival of more than 8 years [32], there are approximately 2.4 million TIA survivors. In a national survey, one in fifteen of those over 65 years old reported a history of TIA [33], which is equivalent to a prevalence of 2.3 million in older Americans. Based on the prevalence of undiagnosed transient neurological events, the true incidence of TIA may be twice as high as the rates of diagnosis [33]. Based on our review of the National Inpatient Sample for 1997-2003, there were an average of 200,000 hospital admissions for TIA each year, with annual charges climbing quickly in the period to $2.6 billion in 2003.

Composite endpoint of new ischemic vascular events: ischemic stroke, myocardial infarction or ischemic vascular death at 90 days.

Description:

Platelet-Oriented Inhibition in New TIA and minor ischemic stroke (POINT) Trial, is a prospective, randomized, double-blind, multicenter trial with the primary null hypothesis that, in patients with TIA or minor ischemic stroke treated with aspirin 50-325 mg/day, there is no difference in the event-free survival at 90 days in those treated with clopidogrel (600 mg loading dose then 75 mg/day) compared to placebo when subjects are randomized within 12 hours of time last known free of new ischemic symptoms.

Its primary objective is to determine whether clopidogrel 75 mg/day by mouth after a loading dose of 600 mg of clopidogrel is effective in preventing major ischemic vascular events (ischemic stroke, myocardial infarction, and ischemic vascular death) at 90 days when initiated within 12 hours of TIA or minor ischemic stroke onset in patients receiving aspirin 50-325 mg/day (with a dose of 150-200 mg daily for 5 days followed by 75-100 mg daily strongly recommended).

Patients over 18 years of age with high-risk TIA (defined as an ABCD2 score greater than or equal to 4) or minor ischemic stroke (with NIHSS less than or equal to 3) who can be treated within 12 hours of time last known free of new ischemic symptoms will be enrolled.

Subjects will be randomized 1:1 (clopidogrel: placebo), controlling for clinical center. A study participant's eligibility will be determined by site personnel prior to accessing the Randomization Module in the WebDCU™, a web-enabled clinical trials management system that was developed by the NETT Statistics and Data Management Center (SDMC) at Medical University of South Carolina (MUSC).Qualified users will access the Randomization Interface and complete a protocol-specific eligibility checklist. If the Randomization Interface finds the patient to be eligible based on the information provided, a randomization number and a confirmatory e-mail are generated.

Each subject is followed for 90 days from randomization; the trial will be completed in 7 years.

A total of 5,840 patients will be recruited. Recruitment will occur over 90 months, with a goal rate of 0.40 subjects/site/month for US sites, and a goal rate of 0.47 subjects/site/month for OUS sites. Current participating sites can be found at: http://www.pointtrial.org/node/18.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 4881
• Est. completion date: April 9, 2018
• Est. primary completion date: April 9, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Neurological deficit (based on history or exam) attributed to focal brain ischemia and EITHER:

• High risk TIA: Complete resolution of the deficit at the time of randomization AND ABCD2 score of (greater than or equal to) 4 OR

• Minor ischemic stroke: residual deficit with NIHSS of (less than or equal to) 3 at the time of randomization

• Ability to randomize within 12 hours of time last known free of new ischemic symptoms.

• Head CT or MRI ruling out hemorrhage or other pathology, such as vascular malformation, tumor, or abscess, that could explain symptoms or contraindicate therapy.

• Ability to tolerate aspirin at a does of 50-325 mg/day.

Exclusion Criteria

• Age <18 years

• TIA symptoms limited to isolated numbness, isolated visual changes, or isolated dizziness/vertigo.

• In the judgment of the treating physician, a candidate for thrombolysis, endarterectomy or endovascular intervention, unless the subject declines both endarterectomy and endovascular intervention at the time of evaluation for eligibility.

• Receipt of any intravenous or intra-arterial thrombolysis within 1 week prior to index event.

• Gastrointestinal bleed or major surgery within 3 months prior to index event.

• History of nontraumatic intracranial hemorrhage.

• Clear indication for anticoagulation (e.g., warfarin, heparin) anticipated during the study period (atrial fibrillation, mechanical heart valve, deep venous thrombosis, pulmonary embolism, antiphospholipid antibody syndrome, hypercoagulable state).

• Qualifying ischemic event induced by angiography or surgery.

• Severe non-cardiovascular comorbidity with life expectancy <3 months.

• Contraindication to clopidogrel or aspirin.

• Known allergy

• Severe renal (serum creatinine >2 mg/dL or 176.8umol/L) or hepatic insufficiency (prior or concurrent diagnosis, with International Normalized Ratio (INR)>1.5 or any resultant complication, such as variceal bleeding, encephalopathy, or icterus)

• Hemostatic disorder or systemic bleeding in the past 3 months

• Current thrombocytopenia (platelet count <100 x10^9/l) or neutropenia (<1 x10^9/l)

• History of drug-induced hematologic or hepatic abnormalities

• Anticipated requirement for long-term (>7 day) non-study antiplatelet drugs (eg, dipyridamole, clopidogrel, ticlopidine), or Non-steroidal Anti-inflammatory Drugs (NSAIDs) affecting platelet function (such as prior vascular stent or arthritis).

• Inability to swallow medications.

• At risk for pregnancy: premenopausal or post menopausal woman within 12 months of last menses without a negative pregnancy test or not committing to adequate birth control (e.g., oral contraceptive, two methods of barrier birth control, or abstinence).

• Unavailability for follow-up.

• Signed and dated informed consent not obtained from patient.

• Other neurological conditions that would complicate assessment of outcomes during follow-up.

• Ongoing treatment in another study of an investigational therapy that may potentially interact with study drug, or treatment in such a study within the last 7 days.

• Previously enrolled in the POINT study.

Related Conditions & MeSH terms

• Ischemia
• Ischemic Attack, Transient

Intervention

Drug:
• Clopidogrel
Loading dose of 600mg followed by 75 milligrams, oral, one tablet daily for 89 days
• placebo
Loading dose of 8 tablets followed by one tablet daily for 89 days

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Box Hill Hospital	Box Hill	Victoria
Australia	Monash Medical Centre	Clayton	Victoria
Australia	The Northern Hospital	Epping	Victoria
Australia	Footscray Hospital	Footscray	Victoria
Australia	Gosford Hospital	Gosford	New South Wales
Australia	Austin Hospital	Heidelberg	Victoria
Australia	John Hunter Hospital	New Lambton	New South Wales
Australia	Royal Melbourne Hospital	Parkville	Victoria
Canada	University of Calgary - Foothills Campus	Calgary	Alberta
Canada	Grey Nuns Hospital	Edmonton	Alberta
Canada	University of Alberta Hospital	Edmonton	Alberta
Canada	Charles LeMoyne Hospital	Greenfield Park	Quebec
Canada	London Health Sciences Center	London	Ontario
Canada	Montreal General Hospital	Montreal	Quebec
Canada	Notre-Dame Hospital	Montreal	Quebec
Canada	Enfant-Jesus Hospital	Quebec
Canada	Vancouver General Hospital	Vancouver	British Columbia
Finland	Helsinki University Central Hospital	Helsinki
Finland	Turku University Hospital	Turku
France	Fleyriat Hospital	Bourg-en-Bresse
France	Pierre Wetheimer Hospital	Bron
France	Adolphe de Rothschild Ophthalmologic Foundation	Paris
France	Bichat-Claude Bernard Hospital	Paris
France	Pitie-Salpetriere Hospital	Paris
France	Foch Hospital	Suresnes
Germany	Neurological Clinic Bad Neustadt	Bad Neustadt an der Saale
Germany	Vivantes Hospital Neukolln	Berlin
Germany	Central Bremen Hospital	Bremen
Germany	University Hospital Essen	Essen
Germany	University Hospital Frankfurt	Frankfurt
Germany	University Medical Center Hamburg	Hamburg
Germany	Hannover Medical School	Hannover
Germany	University Hospital Heidelberg	Heidelberg
Germany	University Hospital Schleswig-Holstein Kiel Campus	Kiel
Germany	University Medical Center Leipzig	Leipzig
Germany	University Hospital Munster	Munster
Germany	University Hospital of Ulm	Ulm	Baden-Württemberg
Mexico	Culiacan General Hospital	Culiacan	Sinaloa
Mexico	Neurosciences Clinical Trials	Culiacan	Sinaloa
Mexico	ABC Medical Center Santa Fe	Mexico City
Mexico	Mexican Association for Clinical Research	Pachuca	Hidalgo
Mexico	Central Hospital Dr. Ignacio Morones Prieto	San Luis Potosí	San Luis Potosi
New Zealand	Auckland City Hospital	Auckland
Spain	Hospital del Mar	Barcelona
Spain	Santa Creu and Sant Pau Hospital	Barcelona
Spain	Vall d'Hebron Hospital	Barcelona
Spain	Basurto Hospital	Bilbao
Spain	Burgos University Hospital	Burgos
Spain	Hospital Donostia	Donostia
Spain	Girona University HOspital	Girona
Spain	La Fe University Hospital	Valencia
Spain	Miguel Servet Hospital	Zaragoza
United Kingdom	Addenbrooke's Hospital	Cambridge
United Kingdom	Queen Elizabeth University Hospital	Glasgow
United Kingdom	Northwick Park Hospital	Harrow
United Kingdom	The Royal London Hospital	London
United Kingdom	University College Hospital	London
United Kingdom	Luton and Dunstable University Hospital	Luton
United Kingdom	John Radcliffe Hospital	Oxford
United Kingdom	Royal United Hospital - Bath	Somerset
United Kingdom	Southampton General Hospital	Southampton
United Kingdom	Royal Stoke University Hospital	Stoke-on-Trent
United States	Abington Memorial Hospital	Abington	Pennsylvania
United States	Summa Akron City Hospital	Akron	Ohio
United States	Lehigh Valley Hospital	Allentown	Pennsylvania
United States	Emory University Hospital	Atlanta	Georgia
United States	Emory University Hospital Midtown	Atlanta	Georgia
United States	Grady Memorial Hospital	Atlanta	Georgia
United States	Augusta University Medical Center	Augusta	Georgia
United States	University of Colorado Hospital	Aurora	Colorado
United States	Seton Medical Center	Austin	Texas
United States	University Medical Center Brackenridge	Austin	Texas
United States	University of Maryland Medical Center	Baltimore	Maryland
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Boston Medical Center	Boston	Massachusetts
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Lincoln Medical and Mental Health Center	Bronx	New York
United States	Kings County Hospital Center	Brooklyn	New York
United States	Maimonides Medical Center	Brooklyn	New York
United States	SUNY Downstate Medical Center	Brooklyn	New York
United States	Buffalo General Medical Center	Buffalo	New York
United States	Cooper University Hospital	Camden	New Jersey
United States	Mercy San Juan Medical Center	Carmichael	California
United States	Chandler Regional Medical Center	Chandler	Arizona
United States	Medical University of South Carolina University Hospital	Charleston	South Carolina
United States	UVA Medical Center	Charlottesville	Virginia
United States	Northwestern Memorial Hospital	Chicago	Illinois
United States	Rush University Medical Center	Chicago	Illinois
United States	University of Illinois Hospital	Chicago	Illinois
United States	Bethesda North Hospital	Cincinnati	Ohio
United States	Christ Hospital	Cincinnati	Ohio
United States	Good Samaritan Hospital	Cincinnati	Ohio
United States	Jewish Hospital	Cincinnati	Ohio
United States	Mercy Health West Hospital	Cincinnati	Ohio
United States	University of Cincinnati Medical Center	Cincinnati	Ohio
United States	Cleveland Clinic	Cleveland	Ohio
United States	MetroHealth Medical Center	Cleveland	Ohio
United States	Palmetto Health Richland	Columbia	South Carolina
United States	Mount Carmel East Hospital	Columbus	Ohio
United States	OSU Wexner Medical Center	Columbus	Ohio
United States	Texas Health Presbyterian Hospital - Dallas	Dallas	Texas
United States	Miami Valley Hospital	Dayton	Ohio
United States	Detroit Receiving Hospital	Detroit	Michigan
United States	Harper University Hospital	Detroit	Michigan
United States	Henry Ford Hospital	Detroit	Michigan
United States	Sinai-Grace Hospital	Detroit	Michigan
United States	St. John Hospital and Medical Center	Detroit	Michigan
United States	St. Elizabeth Medical Center South	Edgewood	Kentucky
United States	Fairview Southdale Hospital	Edina	Minnesota
United States	JFK Medical Center	Edison	New Jersey
United States	Alexian Brothers Medical Center	Elk Grove Village	Illinois
United States	Swedish Medical Center	Englewood	Colorado
United States	Evanston Hospital	Evanston	Illinois
United States	St. Elizabeth Hospital	Florence	Kentucky
United States	St. Elizabeth Hospital Fort Thomas	Fort Thomas	Kentucky
United States	Frederick Memorial Hospital	Frederick	Maryland
United States	UF Health Shands Hospital	Gainesville	Florida
United States	NorthShore Glenbrook Hospital	Glenview	Illinois
United States	Mercy Health Saint Mary's	Grand Rapids	Michigan
United States	Benefis Hospitals Inc	Great Falls	Montana
United States	Great Falls Clinic Hospital, Great Falls	Great Falls	Montana
United States	Guilford Neurologic Associates	Greensboro	North Carolina
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Valley Baptist Medical Center - Harlingen	Harlingen	Texas
United States	Pennsylvania State Hershey Medical Center	Hershey	Pennsylvania
United States	the Queen's Medical Center	Honolulu	Hawaii
United States	Ben Taub General Hospital	Houston	Texas
United States	Houston Methodist Hospital	Houston	Texas
United States	Memorial Hermann Texas Medical Center	Houston	Texas
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	University of Florida	Jacksonville	Florida
United States	Presence Saint Joseph Medical Center	Joliet	Illinois
United States	University of Kansas Hospital	Kansas City	Kansas
United States	UCSD Health La Jolla	La Jolla	California
United States	St. Anthony Hospital	Lakewood	Colorado
United States	Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire
United States	University of Kentucky Hospital	Lexington	Kentucky
United States	Loma Linda University Medical Center	Loma Linda	California
United States	Long Beach Memorial Medical Center	Long Beach	California
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	Kaiser Permanente Los Angeles Medical Center	Los Angeles	California
United States	Ronald Reagan UCLA Medical Center	Los Angeles	California
United States	University of Louisville Hospital	Louisville	Kentucky
United States	Loyola University Medical Center	Maywood	Illinois
United States	Aurora St. Luke's Medical Center	Milwaukee	Wisconsin
United States	Columbia St. Mary's Hospital	Milwaukee	Wisconsin
United States	Froedtert Memorial Lutheran Hospital	Milwaukee	Wisconsin
United States	Abbott Northwestern Hospital	Minneapolis	Minnesota
United States	Hennepin County Medical Center	Minneapolis	Minnesota
United States	University of Minnesota Medical Center Hospital	Minneapolis	Minnesota
United States	WVU Healthcare Ruby Memorial Hospital	Morgantown	West Virginia
United States	Vanderbilt University Hospital	Nashville	Tennessee
United States	Jersey Shore University Medical Center	Neptune	New Jersey
United States	Robert Wood Johnson University Hospital	New Brunswick	New Jersey
United States	Yale-New Haven Hospital	New Haven	Connecticut
United States	New York Presbyterian / Columbia University Medical Center	New York	New York
United States	NYP Weill Cornell Medical Center	New York	New York
United States	Christiana Hospital	Newark	Delaware
United States	Desert Regional Medical Center	Palm Springs	California
United States	Huntington Memorial Hospital	Pasadena	California
United States	Hahnemann University Hospital	Philadelphia	Pennsylvania
United States	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania
United States	Penn Presbyterian Medical Center	Philadelphia	Pennsylvania
United States	Pennsylvania Hospital	Philadelphia	Pennsylvania
United States	Temple University Hospital	Philadelphia	Pennsylvania
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	UPMC Presbyterian Hospital	Pittsburgh	Pennsylvania
United States	UPMC Shadyside Hospital	Pittsburgh	Pennsylvania
United States	Oregon Health and Science University Hospital	Portland	Oregon
United States	Portland VA Medical Center	Portland	Oregon
United States	Providence Portland Medical Center	Portland	Oregon
United States	Providence St. Vincent Medical Center	Portland	Oregon
United States	Rhode Island Hospital	Providence	Rhode Island
United States	Bon Secours St. Francis Medical Center	Richmond	Virginia
United States	Bon Secours St. Mary's Hospital	Richmond	Virginia
United States	Henrico Doctors' Hospital - Forest Campus	Richmond	Virginia
United States	Henrico Doctors' Hospital - Parham Campus	Richmond	Virginia
United States	Mayo Clinic Saint Mary's Campus	Rochester	Minnesota
United States	Rochester General Hospital	Rochester	New York
United States	Strong Memorial Hospital	Rochester	New York
United States	William Beaumont Hospital	Royal Oak	Michigan
United States	Mercy General Hospital	Sacramento	California
United States	UC Davis Medical Center	Sacramento	California
United States	Barnes Jewish Hospital	Saint Louis	Missouri
United States	Mercy Hospital	Saint Louis	Missouri
United States	United Hospital	Saint Paul	Minnesota
United States	University of Texas Health Science Center San Antonio	San Antonio	Texas
United States	Scripps Mercy Hospital San Diego	San Diego	California
United States	UCSD Medical Center - Hillcrest Hospital	San Diego	California
United States	San Francisco General Hospital	San Francisco	California
United States	UCSF Medical Center	San Francisco	California
United States	Sarasota Memorial Hospital	Sarasota	Florida
United States	Harborview Medical Center	Seattle	Washington
United States	University of Washington Medical Center	Seattle	Washington
United States	Mercy Hospital	Springfield	Missouri
United States	Southern Illinois University Memorial Medical Center	Springfield	Illinois
United States	Stanford University Medical Center	Stanford	California
United States	Stony Brook University Hospital	Stony Brook	New York
United States	SUNY Upstate Medical University	Syracuse	New York
United States	Los Robles Hospital and Medical Center	Thousand Oaks	California
United States	University of Toledo Medical Center	Toledo	Ohio
United States	William Beaumont Hospital - Troy	Troy	Michigan
United States	Banner University Medical Center - Tucson Campus	Tucson	Arizona
United States	George Washington University Hospital	Washington	District of Columbia
United States	Henry Ford West Bloomfield Hospital	West Bloomfield	Michigan
United States	Wake Forest Baptist Medical Center	Winston-Salem	North Carolina
United States	UMASS Memorial Medical Center	Worcester	Massachusetts
United States	WellSpan York Hospital	York	Pennsylvania

Sponsors (4)

Lead Sponsor	Collaborator
University of California, San Francisco	Medical University of South Carolina, Neurological Emergencies Treatment Trials Network (NETT), The EMMES Corporation

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Finland,  France,  Germany,  Mexico,  New Zealand,  Spain,  United Kingdom, 

References & Publications (49)

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* Note: There are 49 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Hemorrhagic Stroke	Other safety outcome: Number of participants with Hemorrhagic stroke	up to 90 days
Other	Symptomatic Intracerebral Hemorrhage	Other safety outcome: Number of participants with Symptomatic intracerebral hemorrhage	up to 90 days
Other	Other Symptomatic Intracranial Hemorrhage	Other safety outcome: Number of participants with other symptomatic intracranial hemorrhage	up to 90 days
Other	Major Hemorrhage Other Than Intracranial Hemorrhage	Other safety outcome: Number of Participants with Major hemorrhage other than intracranial hemorrhage	up to 90 days
Other	Minor Hemorrhage	Other safety outcome:Number of Participants with Minor hemorrhage	up to 90 days
Other	Death From Any Cause	Other safety outcome: Number of Participants with Death from any cause	up to 90 days
Primary	Composite of Ischemic Stroke, Myocardial Infarction, or Death From Ischemic Vascular Causes	Primary efficacy outcome: Number of Participants with Ischemic Stroke, Myocardial Infarction, or Death From Ischemic Vascular Causes	Up to 90 days
Primary	Major Hemorrhage	Primary safety outcome: Number of Participants with major hemorrhage	Up to 90 days
Secondary	Ischemic Stroke	Secondary efficacy outcome:Number of participants with Ischemic stroke	Up to 90 days
Secondary	Myocardial Infarction	Secondary efficacy outcome: Number of participants with Myocardial infarction	Up to 90 days
Secondary	Death From Ischemic Vascular Causes	Secondary efficacy outcome: Number of participants with Death from ischemic vascular causes	Up to 90 days
Secondary	Ischemic or Hemorrhagic Stroke	Secondary efficacy outcome: Number of participants with Ischemic or hemorrhagic stroke	Up to 90 days
Secondary	Composite of Ischemic Stroke, Myocardial Infarction, Death From Ischemic Vascular Causes, or Major Hemorrhage	Secondary efficacy outcome: Number of participants with ischemic stroke, myocardial infarction, death from ischemic vascular causes, or major hemorrhage	Up to 90 days